Prof. Dr. Steffen Gay
Name of the Institution
Center of Experimental Rheumatology
Department of Rheumatology
+41-44-255 57 37
+41-44-255 41 70
Group Members Experimental Rheumatology
Renate E. Gay MD, Professor, firstname.lastname@example.org
Michel Neidhart PhD, Professor, Oberassistent, email@example.com
Oliver Distler MD, Professor, Leitender Arzt, firstname.lastname@example.org
Adrian Ciurea MD, PD, email@example.com
Borbala Aradi, MD, Postdoc, firstname.lastname@example.org
Mojca Frank, MD, PhD, Postdoc, email@example.com
Suzana Jordan, PhD, Postdoc, firstname.lastname@example.org
Astrid Jüngel, PhD, PD, email@example.com
Emmanuel Karouzakis, PhD, Postdoc, firstname.lastname@example.org
Kerstin Klein, PhD, Postdoc, email@example.com
Christoph Kolling, MD, Postdoc, Christoph.Kolling@kws.ch
Britta Maurer, MD, Senior-Postdoc, firstname.lastname@example.org
Caroline Ospelt, MD, PhD, email@example.com
Lenka Plestilova, MD, Postdoc, firstname.lastname@example.org
Peter Künzler, MSc, Lab Manager, email@example.com
Maria Comazzi, Histology Technician, firstname.lastname@example.org
Benvinda Henriques, Lab support, email@example.com
Christoph Rudolf, Accounting, firstname.lastname@example.org
Fabienne Wullschleger, Accounting, email@example.com
Tiffany Cheok, Secretary, firstname.lastname@example.org
Georgina Mathis-Pairo, Secretary, email@example.com
Group Members Research of Systemic Autoimmune Diseases
Distler Oliver MD, Professor, firstname.lastname@example.org
Group leader Research of Systemic Autoimmune Diseases
Jüngel Astrid, PD Dr. rer. nat., Senior Scientist, email@example.com
Jordan Suzana, Dr., Clinical Investigator, firstname.lastname@example.org
Dobrota Rucsandra MD, Clinical Science Research Fellow, email@example.com
Horai Yoshiro, Research Fellow, firstname.lastname@example.org
Zhongning Guo, Dr., Research Technician, email@example.com
Kozlova Anastasiia, PhD student, firstname.lastname@example.org
Pachera Elena, PhD student, email@example.com
Renoux Florian, PhD student, firstname.lastname@example.org
Rudnik Michal, PhD student, email@example.com
Schniering Janine, PhD student, firstname.lastname@example.org
Stellato Mara, PhD student, email@example.com
Schneider Nicole, Administration, firstname.lastname@example.org
Current fields of research Experimental Rheumatology
Epigenetic modifications in rheumatic and cardiovascular diseases including methylation, acetylation, sumoylation and microRNA, represent the major focus of our current research.
The molecular and cellular basis of joint destruction in rheumatoid arthritis, osteoarthritis and ankylosing spondylitis, involves especially the search for novel genes and their signaling pathways (“Functional Genomics”).
The laboratory explores the molecular and cellular mechanisms by studying the processes of synovial adhesion to cartilage and bone, the activation of synovial cells to invade and the cellular interactions with cells of the immune system. The role of microparticles and modulating gene expression are another focus of our interest.
Suppressive subtractive hybridization and arrays are used to establish cDNA libraries of genes which are induced by various stimuli, including signaling via cytokine receptors and TOLL-like receptors.
Somatic gene transfer is applied to inhibit synovial cell-mediated cartilage destruction in the SCID mouse model engrafted with normal human cartilage and rheumatoid synovial tissues or isolated cells. Anti-sense constructs, ribozymes , siRNA and antagomirs are used to identify specific targets for future therapeutical interventions. The model is further used to explore the effect of novel drugs from the pharmaceutical industry.
In close cooperation with the Department of Cardiology at the University Hospital of Zürich, we are studying the endothelial function in both rheumatic and cardiovascular patients. Novel investigations on fresh thrombi retrieved from myocardial infarcted patients explore the role of inflammation in the acute coronary syndrome.
A new clinical Research Program has been developed entitled “Molecular Analysis of Gene Expression modulated by Novel Drug Therapies” to study the molecular effects of drugs on individual cells. By evaluating most comprehensively these changes, novel modes of action as well as unwanted side effects can be discovered to develop safer therapeutics.
Current fields of research Systemic Autoimmune Diseases
We are focusing on two connective tissue diseases, systemic sclerosis and inflammatory myopathy. It is one of the internationally leading scleroderma research centers. It has research programs both in clinical research as well as in basic science research.
Systemic sclerosis (SSc) is an autoimmune disease characterized by widespread vasculopathy, inflammation and fibrosis of skin and internal organs. This leads to thickening of the skin as well as irreversible functional impairment of organ function. However the etiology of SSc is unclear and the molecular mechanisms underlying the disease are poorly understood. In several independent but cooperative projects, we aim to determine molecular mechanisms that drive the onset and progression of fibrosis in SSc skin or internal organs.
The term inflammatory myopathy (myositis) comprises a group of heterogeneous autoimmune diseases which are characterized by the presence of an inflammatory infiltrate within the muscle tissue. The skin, the musculoskeletal system, but also internal organs such as lung, heart, or gastrointestinal tract might also be affected. Thus, those orphan diseases have a high morbidity and a significantly increased mortality. Current research efforts in basic science are aimed at the identification of molecular key players of disease pathogenesis as potential therapeutic targets.
Special Techniques and Equipment
In vitro assays and the SCID mouse model of cartilage destruction
Ex vivo gene transfer to synovial cells
Suppressive subtractive hybridization and gene arrays
Education and Training
We have established a molecular biology training course, twice a year, to train new international research fellows in cloning, sequencing, cell-culture, cell-sorting (FACS), TaqMan Real Time PCR, primer design, in situ PCR, in situ hybridization , analysis of acetylation, methylation and miRNAs and immunohistology.
- Iwamoto N, Vettori S, Maurer B, Brock M, Pachera E, Jüngel A, Calcagni M, Gay RE, Whitfield ML, Distler JH, Gay S, Distler O. Downregulation of miR-193b in systemic sclerosis regulates the proliferative vasculopathy by urokinase-type plasminogen activator expression. Ann Rheum Dis. 2014 [Epub ahead of print]
- Kurinna S, Schäfer M, Ostano P, Karouzakis E, Chiorino G, Bloch W, Bachmann A, Gay S, Garrod D, Lefort K, Dotto GP, Beer HD, Werner S. A novel Nrf2-miR-29-desmocollin-2 axis regulates desmosome function in keratinocytes. Nat Commun 5:5099, 2014
- Neidhart M, Karouzakis E, Jüngel A, Gay RE, Gay S. Inhibition of spermidine/spermine N1-acetyltransferase (SSAT1) activity - a new therapeutical concept in rheumatoid arthritis. Arthritis Rheumatol 66:1723-1733, 2014
- Shah N, Hülsmeier AJ, Hochhold N, Neidhart M, Gay S, Hennet T. Exposure to mimivirus collagen promotes arthritis. J Virol 88:838-45, 2014
- Brock M, Samillan VJ, Trenkmann M, Schwarzwald C, Ulrich S, Gay RE, Gassmann M, Ostergaard L, Gay S, Speich R, Huber LC. AntagomiR directed against miR-20a restores functional BMPR2 signalling and prevents vascular remodelling in hypoxia-induced pulmonary hypertension. Eur Heart J 35:3203-11, 2014
- Maurer B, Graf N, Michel BA, Müller-Ladner U, Czirják L, Denton C, Tyndall A, Baron M, Metzig C, Lanius V, Khanna D, Distler O, and EUSTAR co-authors. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database. Ann Rheum Dis.2014. [Epub ahead of print]
- Jordan S, Distler JHW, Maurer B, Huscher D, van Laar JM, Allanore Y, Distler O. Effects and safety of Rituximab in Systemic Sclerosis: An analysis from the European Scleroderma Trial and Research group (EUSTAR). Ann Rheum Dis 2014 [Epub ahead of print]
- Frank S, Peters MA, Wehmeyer C, Strietholt S, Koers-Wunrau C, Bertrand J, Heitzmann M, Hillmann A, Sherwood J, Seyfert C, Gay S, Pap T. Regulation of matrixmetalloproteinase-3 and matrix-metalloproteinase-13 by SUMO-2/3 through the transcription factor NF-κB. Ann Rheum Dis 72:1874-1881, 2013
- Maurer B, Distler A, Suliman YA, Gay RE, Michel BA, Gay S, Distler JHW, Distler O. Vascular endothelial growth factor aggravates fibrosis and vasculopathy in experimental models of systemic sclerosis. Ann Rheum Dis Ann Rheum Dis 73:1880-7, 2014 [Epub 2013]
- Maurer B, Distler A, Dees C, Khan K, Denton CP, Abraham D, Gay RE, Michel BA, Gay S, HW Distler J, Distler O. Levels of target activation predict antifibrotic responses to tyrosine kinase inhibitors. Ann Rheum Dis. 2013;72(12):2039-46
- Gerlag DM, Raza K, van Baarsen LG, Brouwer E, Buckley CD, Burmester GR, Gabay C, Catrina AI, Cope AP, Cornelis F, Dahlqvist SR, Emery P, Eyre S, Finckh A, Gay S, Hazes JM, van der Helm-van Mil A, Huizinga TW, Klareskog L, Kvien TK, Lewis C, Machold KP, Rönnelid J, Schaardenburg DV, Schett G, Smolen JS, Thomas S, Worthington J, Tak PP. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis 71:638-41, 2012
- Nikitopoulou I, Oikonomou N, Karouzakis E, Sevastou I, Nikolaidou-Katsaridou N, Zhao Z, Mersinias V, Armaka M, Xu Y, Masu M, Mills GB, Gay S, Kollias G, Aidinis V. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis. J Exp Med 209:925-33, 2012
IF: IF: 13.853
- Maurer B, Reich N, Juengel A, Kriegsmann J, Gay RE, Schett G, Michel BA, Gay S, Distler JH, Distler O. Fra-2 transgenic mice as a novel model of pulmonary hypertension associated with systemic sclerosis. Ann Rheum Dis. 2012;71(8):1382-7
- Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci USA 108(27):11193-8, 2011
- Dees C, Akhmetshina A, Zerr P, Reich N, Palumbo K, Horn A, Jüngel A, Beyer C, Krönke G, Zwerina J, Reiter R, Alenina N, Maroteaux L, Gay S, Schett G, Distler O, Distler JH. Platelet-derived serotonin links vascular disease and tissue fibrosis. J Exp Med 208(5):961-72, 2011
- Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JHW, Gay S, Distler O. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum. 2010;62(6):1733-43
- Reich N, Maurer B, Akhmetshina A, Venalis P, Dees C, Zerr P, Palumbo K, Zwerina J, Nevskaja T, Gay S, Distler O, Schett G, Distler JH. The transcription factor Fra-2 regulates the production of extracellular matrix in systemic sclerosis. Arthritis Rheum. 2010;62(1):280-90
- Maurer B, Busch N, Jüngel A, Pileckyte M, Gay RE, Michel BA, Schett G, Gay S, Distler J, Distler O. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis. Circulation. 2009;120(23):2367-76
EC Masterswitch 2008-2013
IAR (Institute for Arthritis Research) 2010-2016
EC BTCure 2011-2016
EC FP7-People-2011 Networks for Initial Training (ITN) Marie Curie Osteoimmune 2012-2016
EC Health 2012 Innovation Euro-TEAM 2012-2016
Foreign Government Exchange Agencies